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通过转化生长因子β1转基因表达实现乳腺肿瘤抑制

Mammary tumor suppression by transforming growth factor beta 1 transgene expression.

作者信息

Pierce D F, Gorska A E, Chytil A, Meise K S, Page D L, Coffey R J, Moses H L

机构信息

Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232-2175, USA.

出版信息

Proc Natl Acad Sci U S A. 1995 May 9;92(10):4254-8. doi: 10.1073/pnas.92.10.4254.

DOI:10.1073/pnas.92.10.4254
PMID:7753792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC41922/
Abstract

In cell culture, type alpha transforming growth factor (TGF-alpha) stimulates epithelial cell growth, whereas TGF-beta 1 overrides this stimulatory effect and is growth inhibitory. Transgenic mice that overexpress TGF-alpha under control of the mouse mammary tumor virus (MMTV) promoter/enhancer exhibit mammary ductal hyperplasia and stochastic development of mammary carcinomas, a process that can be accelerated by administration of the chemical carcinogen 7,12-dimethylbenz[a]anthracene. MMTV-TGF-beta 1 transgenic mice display mammary ductal hypoplasia and do not develop mammary tumors. We report that in crossbreeding experiments involving the production of mice carrying both the MMTV-TGF-beta 1 and MMTV-TGF-alpha transgenes, there is marked suppression of mammary tumor formation and that MMTV-TGF-beta 1 transgenic mice are resistant to 7,12-dimethylbenz[a]anthracene-induced mammary tumor formation. These data demonstrate that overexpression of TGF-beta 1 in vivo can markedly suppress mammary tumor development.

摘要

在细胞培养中，α型转化生长因子（TGF-α）可刺激上皮细胞生长，而TGF-β1则会抑制这种刺激作用并具有生长抑制性。在小鼠乳腺肿瘤病毒（MMTV）启动子/增强子控制下过表达TGF-α的转基因小鼠表现出乳腺导管增生和乳腺癌的随机发生，通过给予化学致癌物7,12-二甲基苯并[a]蒽可加速这一过程。MMTV-TGF-β1转基因小鼠表现出乳腺导管发育不全，且不会发生乳腺肿瘤。我们报道，在涉及培育同时携带MMTV-TGF-β1和MMTV-TGF-α转基因小鼠的杂交实验中，乳腺肿瘤形成受到显著抑制，并且MMTV-TGF-β1转基因小鼠对7,12-二甲基苯并[a]蒽诱导的乳腺肿瘤形成具有抗性。这些数据表明，体内TGF-β1的过表达可显著抑制乳腺肿瘤的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab14/41922/30b0402dd4cf/pnas01486-0192-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab14/41922/af8209811f8b/pnas01486-0191-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab14/41922/30b0402dd4cf/pnas01486-0192-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab14/41922/af8209811f8b/pnas01486-0191-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab14/41922/30b0402dd4cf/pnas01486-0192-a.jpg

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